rs35077384

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001385875.1(ZFYVE27):c.572G>T(p.Gly191Val) variant causes a missense change. The variant allele was found at a frequency of 0.0103 in 1,614,016 control chromosomes in the GnomAD database, including 262 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.025 ( 112 hom., cov: 33)

Exomes 𝑓: 0.0087 ( 150 hom. )

Consequence

ZFYVE27
NM_001385875.1 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:8

Conservation

PhyloP100: 3.60

Publications

25 publications found

Variant links:

Genes affected

ZFYVE27 (HGNC:26559): (zinc finger FYVE-type containing 27) This gene encodes a protein with several transmembrane domains, a Rab11-binding domain and a lipid-binding FYVE finger domain. The encoded protein appears to promote neurite formation. A mutation in this gene has been reported to be associated with hereditary spastic paraplegia, however the pathogenicity of the mutation, which may simply represent a polymorphism, is unclear. [provided by RefSeq, Mar 2010]

ZFYVE27 Gene-Disease associations (from GenCC):

hereditary spastic paraplegia 33
Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ZFYVE27 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030166805).

BP6

Variant 10-97749494-G-T is Benign according to our data. Variant chr10-97749494-G-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1289.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFYVE27	NM_001385875.1 link	c.572G>T	p.Gly191Val	missense_variant	Exon 6 of 13	ENST00000684270.1	NP_001372804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFYVE27	ENST00000684270.1 link	c.572G>T	p.Gly191Val	missense_variant	Exon 6 of 13		NM_001385875.1	ENSP00000506975.1

Frequencies

GnomAD3 genomes

AF:

0.0255

AC:

3877

AN:

152126

Hom.:

112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0740

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0129

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00482

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00748

Gnomad OTH

AF:

0.0225

GnomAD2 exomes

AF:

0.00987

AC:

2483

AN:

251480

AF XY:

0.00880

show subpopulations

Gnomad AFR exome

AF:

0.0792

Gnomad AMR exome

AF:

0.00572

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00174

Gnomad FIN exome

AF:

0.00152

Gnomad NFE exome

AF:

0.00638

Gnomad OTH exome

AF:

0.00993

GnomAD4 exome

AF:

0.00871

AC:

12733

AN:

1461772

Hom.:

150

Cov.:

AF XY:

0.00842

AC XY:

6122

AN XY:

727190

show subpopulations

African (AFR)

AF:

0.0786

AC:

2630

AN:

33468

American (AMR)

AF:

0.00642

AC:

287

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.000306

AC:

AN:

26136

East Asian (EAS)

AF:

0.00705

AC:

280

AN:

39700

South Asian (SAS)

AF:

0.00485

AC:

418

AN:

86256

European-Finnish (FIN)

AF:

0.00135

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00745

AC:

8289

AN:

1111914

Other (OTH)

AF:

0.0111

AC:

670

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

661

1322

1984

2645

3306

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

366

732

1098

1464

1830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0255

AC:

3880

AN:

152244

Hom.:

112

Cov.:

AF XY:

0.0238

AC XY:

1771

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0739

AC:

3071

AN:

41530

American (AMR)

AF:

0.0129

AC:

197

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00483

AC:

AN:

5178

South Asian (SAS)

AF:

0.00352

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000848

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00747

AC:

508

AN:

68020

Other (OTH)

AF:

0.0218

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

191

382

572

763

954

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0133

Hom.:

161

Bravo

AF:

0.0286

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.0726

AC:

320

ESP6500EA

AF:

0.00767

AC:

ExAC

AF:

0.0109

AC:

1329

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.00905

EpiControl

AF:

0.00812

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3Benign:8

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 33

Uncertain:2Benign:2

Jan 01, 2016

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was classified as: Uncertain significance. -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

May 09, 2014

OMIM

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 25, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spastic paraplegia

Benign:2

Apr 16, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spastic tetraparesis

Uncertain:1

Nov 28, 2013

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jan 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 18606302, 20981092, 16826525, 27884173) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.090

.;.;.;.;T;.;.

Eigen

Benign

-0.016

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.92

D;D;D;D;D;D;D

MetaRNN

Benign

0.0030

T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.9

.;.;.;.;L;L;L

PhyloP100

3.6

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.6

D;N;N;N;D;.;N

REVEL

Benign

0.17

Sift

Uncertain

0.0070

D;D;D;D;D;.;D

Sift4G

Benign

0.10

T;T;T;T;T;T;T

Polyphen

0.58, 0.19, 0.29, 0.26

.;.;.;P;B;B;B

Vest4

0.43

ClinPred

0.018

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

gMVP

0.42

Mutation Taster

=88/12

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over